Two forms of mastocytosis have been documented. Ninety percent of our patients have disease presenting initially as urticaria pigmentosa and which slowly progresses over decades. A second repidly progressive form of mastocytosis presents with lymphodenopathy, peripheral eosinophilia, an elevated sedimentation rate, and an elevated alkaline phosphatase. One patient with this disease, which we have termed lymphadenopathic mastocytosis with eosinophilia, has had an initial response to a combination of cytoxan, vincristine, and prednisone. In a related observation, patients with malignancy and mastocytosis are more likely to have oligoclonal immunoglobulin bands on agarose gel electrophoresis, aiding in diagnosis. Patients with systemic mastocytosis have elevated plasma histamine levels (approximately 2000 pg/ml). Patients with urticaria pigmentosa have slightly elevated plasma histamines, while patients with idiopathic anaphylaxis have normal histamines (approximately 270 pg/ml). Systemic mastocytosis may be complicated by an increase in basal acid output, and by maladsorption. Such findings are highly variable, but tend to occur in patients with severe generalized disease. The histamine content increases in cultures of human bone marrow in association with the appearance of poorly defined granulated cells which die out after approximately 6 weeks. Lectin-stimulated human peripheral mononuclear cells produce a factor which stimulates the growth of cultured, IL-3 dependent, mouse mast cells.